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12 results on '"Celmins, D."'

1. Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment

Author

Tuena, C, Maestri, S, Serino, S, Pedroli, E, Stramba-Badiale, M, Riva, G, Silbert, L, Lind, B, Crissey, R, Kaye, J, Carter, R, Dolen, S, Quinn, J, Schneider, L, Pawluczyk, S, Becerra, M, Teodoro, L, Dagerman, K, Spann, B, Brewer, J, Fleisher, A, Vanderswag, H, Ziolkowski, J, Heidebrink, J, Zbizek-Nulph, L, Lord, J, Albers, C, Petersen, R, Mason, S, Knopman, D, Johnson, K, Villanueva-Meyer, J, Pavlik, V, Pacini, N, Lamb, A, Kass, J, Doody, R, Shibley, V, Chowdhury, M, Rountree, S, Dang, M, Stern, Y, Honig, L, Mintz, A, Ances, B, Morris, J, Winkfield, D, Carroll, M, Stobbs-Cucchi, G, Oliver, A, Creech, M, Mintun, M, Schneider, S, Geldmacher, D, Love, M, Griffith, R, Clark, D, Brockington, J, Marson, D, Grossman, H, Goldstein, M, Greenberg, J, Mitsis, E, Shah, R, Lamar, M, Samuels, P, Duara, R, Greig-Custo, M, Rodriguez, R, Albert, M, Onyike, C, Farrington, L, Rudow, S, Brichko, R, Kielb, S, Smith, A, Raj, B, Fargher, K, Sadowski, M, Wisniewski, T, Shulman, M, Faustin, A, Rao, J, Castro, K, Ulysse, A, Chen, S, Doraiswamy, P, Petrella, J, James, O, Wong, T, Borges-Neto, S, Karlawish, J, Wolk, D, Vaishnavi, S, Clark, C, Arnold, S, Smith, C, Jicha, G, Khouli, R, Raslau, F, Lopez, O, Oakley, M, Simpson, D, Porsteinsson, A, Martin, K, Kowalski, N, Keltz, M, Goldstein, B, Makino, K, Ismail, M, Brand, C, Thai, G, Pierce, A, Yanez, B, Sosa, E, Witbracht, M, Kelley, B, Nguyen, T, Womack, K, Mathews, D, Quiceno, M, Levey, A, Lah, J, Hajjar, I, Burns, J, Swerdlow, R, Brooks, W, Silverman, D, Kremen, S, Apostolova, L, Tingus, K, Lu, P, Bartzokis, G, Woo, E, Teng, E, Graff-Radford, N, Parfitt, F, Poki-Walker, K, Farlow, M, Hake, A, Matthews, B, Brosch, J, Herring, S, van Dyck, C, Mecca, A, Good, S, Macavoy, M, Carson, R, Varma, P, Chertkow, H, Vaitekunas, S, Hosein, C, Black, S, Stefanovic, B, Heyn, C, Hsiung, G, Kim, E, Mudge, B, Sossi, V, Feldman, H, Assaly, M, Finger, E, Pasternak, S, Rachinsky, I, Kertesz, A, Drost, D, Rogers, J, Grant, I, Muse, B, Rogalski, E, Robson, J, Mesulam, M, Kerwin, D, Wu, C, Johnson, N, Lipowski, K, Weintraub, S, Bonakdarpour, B, Pomara, N, Hernando, R, Sarrael, A, Rosen, H, Miller, B, Weiner, M, Perry, D, Turner, R, Reynolds, B, Mccann, K, Poe, J, Marshall, G, Sperling, R, Yesavage, J, Taylor, J, Chao, S, Coleman, J, White, J, Lane, B, Rosen, A, Tinklenberg, J, Belden, C, Atri, A, Clark, K, Zamrini, E, Sabbagh, M, Killiany, R, Stern, R, Mez, J, Kowall, N, Budson, A, Obisesan, T, Ntekim, O, Wolday, S, Khan, J, Nwulia, E, Nadarajah, S, Lerner, A, Ogrocki, P, Tatsuoka, C, Fatica, P, Fletcher, E, Maillard, P, Olichney, J, Decarli, C, Carmichael, O, Bates, V, Capote, H, Rainka, M, Borrie, M, Lee, T, Bartha, R, Johnson, S, Asthana, S, Carlsson, C, Perrin, A, Burke, A, Scharre, D, Kataki, M, Tarawneh, R, Hart, D, Zimmerman, E, Celmins, D, Miller, D, Ponto, L, Smith, K, Koleva, H, Shim, H, Nam, K, Schultz, S, Williamson, J, Craft, S, Cleveland, J, Yang, M, Sink, K, Ott, B, Drake, J, Tremont, G, Daiello, L, Ritter, A, Bernick, C, Munic, D, O'Connelll, A, Mintzer, J, Wiliams, A, Masdeu, J, Shi, J, Garcia, A, Newhouse, P, Potkin, S, Salloway, S, Malloy, P, Correia, S, Kittur, S, Pearlson, G, Blank, K, Anderson, K, Flashman, L, Seltzer, M, Hynes, M, Santulli, R, Relkin, N, Chiang, G, Lee, A, Lin, M, Ravdin, L, Tuena C., Maestri S., Serino S., Pedroli E., Stramba-Badiale M., Riva G., Silbert L. C., Lind B., Crissey R., Kaye J. A., Carter R., Dolen S., Quinn J., Schneider L. S., Pawluczyk S., Becerra M., Teodoro L., Dagerman K., Spann B. M., Brewer J., Fleisher A., Vanderswag H., Ziolkowski J., Heidebrink J. L., Zbizek-Nulph L., Lord J. L., Albers C. S., Petersen R., Mason S. S., Knopman D., Johnson K., Villanueva-Meyer J., Pavlik V., Pacini N., Lamb A., Kass J. S., Doody R. S., Shibley V., Chowdhury M., Rountree S., Dang M., Stern Y., Honig L. S., Mintz A., Ances B., Morris J. C., Winkfield D., Carroll M., Stobbs-Cucchi G., Oliver A., Creech M. L., Mintun M. A., Schneider S., Geldmacher D., Love M. N., Griffith R., Clark D., Brockington J., Marson D., Grossman H., Goldstein M. A., Greenberg J., Mitsis E., Shah R. C., Lamar M., Samuels P., Duara R., Greig-Custo M. T., Rodriguez R., Albert M., Onyike C., Farrington L., Rudow S., Brichko R., Kielb S., Smith A., Raj B. A., Fargher K., Sadowski M., Wisniewski T., Shulman M., Faustin A., Rao J., Castro K. M., Ulysse A., Chen S., Doraiswamy P. M., Petrella J. R., James O., Wong T. Z., Borges-Neto S., Karlawish J. H., Wolk D. A., Vaishnavi S., Clark C. M., Arnold S. E., Smith C. D., Jicha G. A., Khouli R. E., Raslau F. D., Lopez O. L., Oakley M. A., Simpson D. M., Porsteinsson A. P., Martin K., Kowalski N., Keltz M., Goldstein B. S., Makino K. M., Ismail M. S., Brand C., Thai G., Pierce A., Yanez B., Sosa E., Witbracht M., Kelley B., Nguyen T., Womack K., Mathews D., Quiceno M., Levey A. I., Lah J. J., Hajjar I., Burns J. M., Swerdlow R. H., Brooks W. M., Silverman D. H. S., Kremen S., Apostolova L., Tingus K., Lu P. H., Bartzokis G., Woo E., Teng E., Graff-Radford N. R., Parfitt F., Poki-Walker K., Farlow M. R., Hake A. M., Matthews B. R., Brosch J. R., Herring S., van Dyck C. H., Mecca A. P., Good S. P., MacAvoy M. G., Carson R. E., Varma P., Chertkow H., Vaitekunas S., Hosein C., Black S., Stefanovic B., Heyn C., Hsiung G. -Y. R., Kim E., Mudge B., Sossi V., Feldman H., Assaly M., Finger E., Pasternak S., Rachinsky I., Kertesz A., Drost D., Rogers J., Grant I., Muse B., Rogalski E., Robson J., Mesulam M. -M., Kerwin D., Wu C. -K., Johnson N., Lipowski K., Weintraub S., Bonakdarpour B., Pomara N., Hernando R., Sarrael A., Rosen H. J., Miller B. L., Weiner M. W., Perry D., Turner R. S., Reynolds B., MCCann K., Poe J., Marshall G. A., Sperling R. A., Johnson K. A., Yesavage J., Taylor J. L., Chao S., Coleman J., White J. D., Lane B., Rosen A., Tinklenberg J., Belden C. M., Atri A., Clark K. A., Zamrini E., Sabbagh M., Killiany R., Stern R., Mez J., Kowall N., Budson A. E., Obisesan T. O., Ntekim O. E., Wolday S., Khan J. I., Nwulia E., Nadarajah S., Lerner A., Ogrocki P., Tatsuoka C., Fatica P., Fletcher E., Maillard P., Olichney J., DeCarli C., Carmichael O., Bates V., Capote H., Rainka M., Borrie M., Lee T. -Y., Bartha R., Johnson S., Asthana S., Carlsson C. M., Perrin A., Burke A., Scharre D. W., Kataki M., Tarawneh R., Hart D., Zimmerman E. A., Celmins D., Miller D. D., Ponto L. L. B., Smith K. E., Koleva H., Shim H., Nam K. W., Schultz S. K., Williamson J. D., Craft S., Cleveland J., Yang M., Sink K. M., Ott B. R., Drake J., Tremont G., Daiello L. A., Drake J. D., Ritter A., Bernick C., Munic D., O'Connelll A., Mintzer J., Wiliams A., Masdeu J., Shi J., Garcia A., Newhouse P., Potkin S., Salloway S., Malloy P., Correia S., Kittur S., Pearlson G. D., Blank K., Anderson K., Flashman L. A., Seltzer M., Hynes M. L., Santulli R. B., Relkin N., Chiang G., Lee A., Lin M., Ravdin L., Tuena, C, Maestri, S, Serino, S, Pedroli, E, Stramba-Badiale, M, Riva, G, Silbert, L, Lind, B, Crissey, R, Kaye, J, Carter, R, Dolen, S, Quinn, J, Schneider, L, Pawluczyk, S, Becerra, M, Teodoro, L, Dagerman, K, Spann, B, Brewer, J, Fleisher, A, Vanderswag, H, Ziolkowski, J, Heidebrink, J, Zbizek-Nulph, L, Lord, J, Albers, C, Petersen, R, Mason, S, Knopman, D, Johnson, K, Villanueva-Meyer, J, Pavlik, V, Pacini, N, Lamb, A, Kass, J, Doody, R, Shibley, V, Chowdhury, M, Rountree, S, Dang, M, Stern, Y, Honig, L, Mintz, A, Ances, B, Morris, J, Winkfield, D, Carroll, M, Stobbs-Cucchi, G, Oliver, A, Creech, M, Mintun, M, Schneider, S, Geldmacher, D, Love, M, Griffith, R, Clark, D, Brockington, J, Marson, D, Grossman, H, Goldstein, M, Greenberg, J, Mitsis, E, Shah, R, Lamar, M, Samuels, P, Duara, R, Greig-Custo, M, Rodriguez, R, Albert, M, Onyike, C, Farrington, L, Rudow, S, Brichko, R, Kielb, S, Smith, A, Raj, B, Fargher, K, Sadowski, M, Wisniewski, T, Shulman, M, Faustin, A, Rao, J, Castro, K, Ulysse, A, Chen, S, Doraiswamy, P, Petrella, J, James, O, Wong, T, Borges-Neto, S, Karlawish, J, Wolk, D, Vaishnavi, S, Clark, C, Arnold, S, Smith, C, Jicha, G, Khouli, R, Raslau, F, Lopez, O, Oakley, M, Simpson, D, Porsteinsson, A, Martin, K, Kowalski, N, Keltz, M, Goldstein, B, Makino, K, Ismail, M, Brand, C, Thai, G, Pierce, A, Yanez, B, Sosa, E, Witbracht, M, Kelley, B, Nguyen, T, Womack, K, Mathews, D, Quiceno, M, Levey, A, Lah, J, Hajjar, I, Burns, J, Swerdlow, R, Brooks, W, Silverman, D, Kremen, S, Apostolova, L, Tingus, K, Lu, P, Bartzokis, G, Woo, E, Teng, E, Graff-Radford, N, Parfitt, F, Poki-Walker, K, Farlow, M, Hake, A, Matthews, B, Brosch, J, Herring, S, van Dyck, C, Mecca, A, Good, S, Macavoy, M, Carson, R, Varma, P, Chertkow, H, Vaitekunas, S, Hosein, C, Black, S, Stefanovic, B, Heyn, C, Hsiung, G, Kim, E, Mudge, B, Sossi, V, Feldman, H, Assaly, M, Finger, E, Pasternak, S, Rachinsky, I, Kertesz, A, Drost, D, Rogers, J, Grant, I, Muse, B, Rogalski, E, Robson, J, Mesulam, M, Kerwin, D, Wu, C, Johnson, N, Lipowski, K, Weintraub, S, Bonakdarpour, B, Pomara, N, Hernando, R, Sarrael, A, Rosen, H, Miller, B, Weiner, M, Perry, D, Turner, R, Reynolds, B, Mccann, K, Poe, J, Marshall, G, Sperling, R, Yesavage, J, Taylor, J, Chao, S, Coleman, J, White, J, Lane, B, Rosen, A, Tinklenberg, J, Belden, C, Atri, A, Clark, K, Zamrini, E, Sabbagh, M, Killiany, R, Stern, R, Mez, J, Kowall, N, Budson, A, Obisesan, T, Ntekim, O, Wolday, S, Khan, J, Nwulia, E, Nadarajah, S, Lerner, A, Ogrocki, P, Tatsuoka, C, Fatica, P, Fletcher, E, Maillard, P, Olichney, J, Decarli, C, Carmichael, O, Bates, V, Capote, H, Rainka, M, Borrie, M, Lee, T, Bartha, R, Johnson, S, Asthana, S, Carlsson, C, Perrin, A, Burke, A, Scharre, D, Kataki, M, Tarawneh, R, Hart, D, Zimmerman, E, Celmins, D, Miller, D, Ponto, L, Smith, K, Koleva, H, Shim, H, Nam, K, Schultz, S, Williamson, J, Craft, S, Cleveland, J, Yang, M, Sink, K, Ott, B, Drake, J, Tremont, G, Daiello, L, Ritter, A, Bernick, C, Munic, D, O'Connelll, A, Mintzer, J, Wiliams, A, Masdeu, J, Shi, J, Garcia, A, Newhouse, P, Potkin, S, Salloway, S, Malloy, P, Correia, S, Kittur, S, Pearlson, G, Blank, K, Anderson, K, Flashman, L, Seltzer, M, Hynes, M, Santulli, R, Relkin, N, Chiang, G, Lee, A, Lin, M, Ravdin, L, Tuena C., Maestri S., Serino S., Pedroli E., Stramba-Badiale M., Riva G., Silbert L. C., Lind B., Crissey R., Kaye J. A., Carter R., Dolen S., Quinn J., Schneider L. S., Pawluczyk S., Becerra M., Teodoro L., Dagerman K., Spann B. M., Brewer J., Fleisher A., Vanderswag H., Ziolkowski J., Heidebrink J. L., Zbizek-Nulph L., Lord J. L., Albers C. S., Petersen R., Mason S. S., Knopman D., Johnson K., Villanueva-Meyer J., Pavlik V., Pacini N., Lamb A., Kass J. S., Doody R. S., Shibley V., Chowdhury M., Rountree S., Dang M., Stern Y., Honig L. S., Mintz A., Ances B., Morris J. C., Winkfield D., Carroll M., Stobbs-Cucchi G., Oliver A., Creech M. L., Mintun M. A., Schneider S., Geldmacher D., Love M. N., Griffith R., Clark D., Brockington J., Marson D., Grossman H., Goldstein M. A., Greenberg J., Mitsis E., Shah R. C., Lamar M., Samuels P., Duara R., Greig-Custo M. T., Rodriguez R., Albert M., Onyike C., Farrington L., Rudow S., Brichko R., Kielb S., Smith A., Raj B. A., Fargher K., Sadowski M., Wisniewski T., Shulman M., Faustin A., Rao J., Castro K. M., Ulysse A., Chen S., Doraiswamy P. M., Petrella J. R., James O., Wong T. Z., Borges-Neto S., Karlawish J. H., Wolk D. A., Vaishnavi S., Clark C. M., Arnold S. E., Smith C. D., Jicha G. A., Khouli R. E., Raslau F. D., Lopez O. L., Oakley M. A., Simpson D. M., Porsteinsson A. P., Martin K., Kowalski N., Keltz M., Goldstein B. S., Makino K. M., Ismail M. S., Brand C., Thai G., Pierce A., Yanez B., Sosa E., Witbracht M., Kelley B., Nguyen T., Womack K., Mathews D., Quiceno M., Levey A. I., Lah J. J., Hajjar I., Burns J. M., Swerdlow R. H., Brooks W. M., Silverman D. H. S., Kremen S., Apostolova L., Tingus K., Lu P. H., Bartzokis G., Woo E., Teng E., Graff-Radford N. R., Parfitt F., Poki-Walker K., Farlow M. R., Hake A. M., Matthews B. R., Brosch J. R., Herring S., van Dyck C. H., Mecca A. P., Good S. P., MacAvoy M. G., Carson R. E., Varma P., Chertkow H., Vaitekunas S., Hosein C., Black S., Stefanovic B., Heyn C., Hsiung G. -Y. R., Kim E., Mudge B., Sossi V., Feldman H., Assaly M., Finger E., Pasternak S., Rachinsky I., Kertesz A., Drost D., Rogers J., Grant I., Muse B., Rogalski E., Robson J., Mesulam M. -M., Kerwin D., Wu C. -K., Johnson N., Lipowski K., Weintraub S., Bonakdarpour B., Pomara N., Hernando R., Sarrael A., Rosen H. J., Miller B. L., Weiner M. W., Perry D., Turner R. S., Reynolds B., MCCann K., Poe J., Marshall G. A., Sperling R. A., Johnson K. A., Yesavage J., Taylor J. L., Chao S., Coleman J., White J. D., Lane B., Rosen A., Tinklenberg J., Belden C. M., Atri A., Clark K. A., Zamrini E., Sabbagh M., Killiany R., Stern R., Mez J., Kowall N., Budson A. E., Obisesan T. O., Ntekim O. E., Wolday S., Khan J. I., Nwulia E., Nadarajah S., Lerner A., Ogrocki P., Tatsuoka C., Fatica P., Fletcher E., Maillard P., Olichney J., DeCarli C., Carmichael O., Bates V., Capote H., Rainka M., Borrie M., Lee T. -Y., Bartha R., Johnson S., Asthana S., Carlsson C. M., Perrin A., Burke A., Scharre D. W., Kataki M., Tarawneh R., Hart D., Zimmerman E. A., Celmins D., Miller D. D., Ponto L. L. B., Smith K. E., Koleva H., Shim H., Nam K. W., Schultz S. K., Williamson J. D., Craft S., Cleveland J., Yang M., Sink K. M., Ott B. R., Drake J., Tremont G., Daiello L. A., Drake J. D., Ritter A., Bernick C., Munic D., O'Connelll A., Mintzer J., Wiliams A., Masdeu J., Shi J., Garcia A., Newhouse P., Potkin S., Salloway S., Malloy P., Correia S., Kittur S., Pearlson G. D., Blank K., Anderson K., Flashman L. A., Seltzer M., Hynes M. L., Santulli R. B., Relkin N., Chiang G., Lee A., Lin M., and Ravdin L.

Abstract

Background: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer’s Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. Methods: Four hundred two individuals with aMCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. Results: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abno

Published
2023

2. A blood-based signature of cerebrospinal fluid A beta(1-42) status

Author

Goudey, B., Fung, B.J., Schieber, C., Faux, N.G., Weiner, M.W., Aisen, P., Petersen, R., Jack, C.R., Jagust, W., Trojanowki, J.Q., Toga, A.W., Beckett, L., Green, R.C., Saykin, A.J., Morris, J., Shaw, L.M., Kaye, J., Quinn, J., Silbert, L., Lind, B., Carter, R., Dolen, S., Schneider, L.S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B.M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J.L., Lord, J.L., Mason, S.S., Albers, C.S., Knopman, D., Johnson, K., Doody, R.S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L.S., Bell, K.L., Ances, B., Morris, J.C., Carroll, M., Creech, M.L., Franklin, E., Mintun, M.A., Schneider, S., Oliver, A., Marson, D., Griffth, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Natelson Love, M., Grossman, H., Mitsis, E., Shah, R.C., deToledo-Morrell, L., Duara, R., Varon, D., Greig, M.T., Roberts, P., Albert, M., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J.E., Cerbone, B., Michel, C.A., Pogorelec, D.M., Rusinek, H., Leon, M.J. de, Glodzik, L., De Santi, S., Doraiswamy, P.M., Petrella, J.R., Borges-Neto, S., Wong, T.Z., Coleman, E., Smith, C.D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Porsteinsson, A.P., Goldstein, B.S., Martin, K., Makino, K.M., Ismail, M.S., Brand, C., Mulnard, R.A., Thai, G., McAdams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Levey, A.I., Lah, J.J., Cellar, J.S., Burns, J.M., Swerdlow, R.H., Brooks, W.M., Apostolova, L., Tingus, K., Woo, E., Silverman, D.H.S., Lu, P.H., Bartzokis, G., Graff-Radford, N.R., Parftt, F., Kendall, T., Johnson, H., Farlow, M.R., Hake, A.M., Matthews, B.R., Brosch, J.R., Herring, S., Hunt, C., Dyck, .H. van, Carson, R.E., MacAvoy, M.G., Varma, P., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, Ging-Yuek Robin, Feldman, H., Mudge, B., Assaly, M., Finger, E., Pasternack, S., Rachisky, I., Trost, D., Kertesz, A., Bernick, C., Munic, D., Mesulam, M.-M., Lipowski, K., Weintraub, S., Bonakdarpour, B., Kerwin, D., Wu, C.-K., Johnson, N., Sadowsky, C., Villena, T., Turner, R.S., Reynolds, B., Sperling, R.A., Johnson, K.A., Marshall, G., Yesavage, J., Taylor, J.L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M.N., Belden, C.M., Jacobson, S.A., Sirrel, S.A., Kowall, N., Killiany, R., Budson, A.E., Norbash, A., Johnson, P.L., Obisesan, T.O., Wolday, S., Allard, J., Lerner, A., Ogrocki, P., Tatsuoka, C., Fatica, P., Fletcher, E., Maillard, P., Olichney, J., DeCarli, C., Carmichael, O., Kittur, S., Borrie, M., Lee, T.-Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C.M., Potkin, S.G., Preda, A., Nguyen, D., Tariot, P., Burke, A., Trncic, N., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D.W., Kataki, M., Adeli, A., Zimmerman, E.A., Celmins, D., Brown, A.D., Pearlson, G.D., Blank, K., Anderson, K., Flashman, L.A., Seltzer, M., Hynes, M.L., Santulli, R.B., Sink, K.M., Gordineer, L., Williamson, J.D., Garg, P., Watkins, F., Ott, B.R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H.J., Miller, B.L., Perry, D., Mintzer, J., Spicer, K., Bachman, D., Pomara, N., Hernando, R., Sarrael, A., Relkin, N., Chaing, G., Lin, M., Ravdin, L., Smith, A., Raj, B.A., Fargher, K., Saykin, A., Nho, K., Kling, M., Toledo, J., Shaw, L., Trojanowski, J., Farrer, L., Kastsenmueller, G., Arnold, M., Wishart, D., Wurtz, P., Bhattcharyya, S., Duijin, C. van, Mangravite, L., Han, X., Hankemeier, T., Fiehn, O., Barupal, D., Thiele, I., Heinken, A., Meikle, P., Price, N., Funk, C., Jia, W., Kueider-Paisley, A., Tenebaum, J., Black, C., Moseley, A., Thompson, W., Mahmoudiandehkorki, S., Baillie, R., Welsh-Bohmer, K., Plassman, B., and Epidemiology

Subjects
Male, 0301 basic medicine, Apolipoprotein E, Oncology, medicine.medical_specialty, Amyloid, Amyloid beta, lcsh:Medicine, Article, 03 medical and health sciences, Apolipoproteins E, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Predictive Value of Tests, Internal medicine, medicine, Humans, Dementia, Cognitive decline, lcsh:Science, Aged, Aged, 80 and over, Amyloid beta-Peptides, Multidisciplinary, biology, Chemokine CCL26, business.industry, lcsh:R, Alzheimer’s Disease Metabolomics Consortium, Alzheimer’s Disease Neuroimaging Initiative, medicine.disease, Peptide Fragments, 3. Good health, 030104 developmental biology, biology.protein, Chromogranin A, Female, lcsh:Q, Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative
Abstract

It is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β1−42 (Aβ1−42) may be an earlier indicator of Alzheimer’s disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual’s CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ1−42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ1−42, Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ1−42 levels and that the resulting model also validates reasonably across PET Aβ1−42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ1−42 status, the earliest risk indicator for AD, with high accuracy.

Published
2019

3. Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

Author

Young, A. L., Marinescu, R. V., Oxtoby, N. P., Bocchetta, M., Yong, K., Firth, N. C., Cash, D. M., Thomas, D. L., Dick, K. M., Cardoso, J., van Swieten, J., Borroni, B., Galimberti, D., Masellis, M., Tartaglia, M. C., Rowe, J. B., Graff, C., Tagliavini, F., Frisoni, G. B., Laforce, R., Finger, E., de Mendonca, A., Sorbi, S., Warren, J. D., Crutch, S., Fox, N. C., Ourselin, S., Schott, J. M., Rohrer, J. D., Alexander, D. C., Andersson, C., Archetti, S., Arighi, A., Benussi, L., Binetti, G., Black, S., Cosseddu, M., Fallstrom, M., Ferreira, C., Fenoglio, C., Freedman, M., Fumagalli, G. G., Gazzina, S., Ghidoni, R., Grisoli, M., Jelic, V., Jiskoot, L., Keren, R., Lombardi, G., Maruta, C., Meeter, L., Mead, S., van Minkelen, R., Nacmias, B., Oijerstedt, L., Padovani, A., Panman, J., Pievani, M., Polito, C., Premi, E., Prioni, S., Rademakers, R., Redaelli, V., Rogaeva, E., Rossi, G., Rossor, M., Scarpini, E., Tang-Wai, D., Thonberg, H., Tiraboschi, P., Verdelho, A., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Thompson, P., Schuff, N., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., de Toledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Wong, T. Z., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M. A., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., Devous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H., P. H., Lu, Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., Macavoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Stefanovic, B., Caldwell, C., Hsiung, G. -Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Bernick, C., Munic, D., Kerwin, D., Mesulam, M. -M., Lipowski, K., C. -K., Wu, Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Fletcher, E., Carmichael, O., Olichney, J., Decarli, C., Kittur, S., Borrie, M., Lee, T. -Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L. L. B., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B. A., Neylan, T., Grafman, J., Davis, M., Morrison, R., Hayes, J., Finley, S., Friedl, K., Fleischman, D., Arfanakis, K., James, O., Massoglia, D., Fruehling, J. J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., and Furst, A. J.

Published
2018

4. Sex-dependent association of common variants of microcephaly genes with brain structure

Author

Rimol, L. M., Agartz, I., Djurovic, S., Brown, A. A., Roddey, J. C., Kahler, A. K., Mattingsdal, M., Athanasiu, L., Joyner, A. H., Schork, N. J., Halgren, E., Sundet, K., Melle, I., Dale, A. M., Andreassen, O. A., Weiner, M., Thal, L., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J., Toga, A. W., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.- Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given II, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Potkin, S. G., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Saykin, A. J., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., Wilks, K. L., and Alzheimer's Disease Neuroimaging Initiative

Subjects
Adult, Male, Microcephaly, Molecular Sequence Data, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Brain mapping, ASPM, Sex Factors, medicine, Animals, Humans, SNP, Genetic Predisposition to Disease, Genetics, Brain Mapping, Multidisciplinary, CDK5RAP2, Brain morphometry, Brain, Middle Aged, Biological Sciences, medicine.disease, Magnetic Resonance Imaging, Phenotype, Brain size, Female
Abstract

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717–728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637–644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2 , MCPH1 , and ASPM , with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample ( n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample ( n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.

Published
2009

5. Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Author

Jahanshad, N., Rajagopalan, P., Hua, X., Hibar, D. P., Nir, T. M., Toga, A. W., Jack, C. R., Saykin, A. J., Green, R. C., Weiner, M. W., Medland, S. E., Montgomery, G. W., Hansell, N. K., McMahon, K. L., de Zubicaray, G. I., Martin, N. G., Wright, M. J., Thompson, P. M., the Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jagust, W., Trojanowski, J. Q., Beckett, L., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., DeCarli, C., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Cairns, N. J., Taylor-Reinwald, L., Trojanowki, J. Q., Shaw, L., Lee, V. M. Y., Korecka, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Khachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, L. S., Pawluczyk, S., Spann, B. M., Brewer, J., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Coleman, R. E., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Lopez, O. L., Oakley, M., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Lu, P. H., Bartzokis, G., Silverman, D. H. S., Graff-Radford, N. R., Parfitt, F., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., van Dyck, C. H., Carson, R. E., MacAvoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, G.-Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, M.-M., Lipowski, K., Wu, C.-K., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Yesavage, J., Taylor, J. L., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Obisesan, T. O., Wolday, S., Bwayo, S. K., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, T.- Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Longmire, C. F., Spicer, K., Finger, E., Rachinsky, I., and Drost, D.

Published
2013
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6. Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans

Author

Bakken, TE, Roddey, JC, Djurovic, S, Akshoomoff, N, Amaral, DG, Bloss, CS, Casey, BJ, Chang, L, Ernst, TM, Gruen, JR, Jernigan, TL, Kaufmann, WE, Kenet, T, Kennedy, DN, Kuperman, JM, Murray, SS, Sowell, ER, Rimol, LM, Mattingsdal, M, Melle, I, Agartz, I, Andreassen, OA, Schork, NJ, Dale, AM, Alzheimer’s Disease Neuroimaging Initiative, Pediatric Imaging, Neurocognition, Genetics Study, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jr, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Liu, E, Montine, T, Gamst, A, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Harvey, D, Kornak, J, Dale, A, Bernstein, M, Felmlee, J, Fox, N, Thompson, P, Schuff, N, Alexander, G, DeCarli, C, Bandy, D, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Cairns, NJ, Taylor-Reinwald, L, Shaw, L, Lee, VM, Korecka, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Kachaturian, Z, Frank, R, Snyder, PJ, Molchan, S, Kaye, J, Quinn, J, Lind, B, Dolen, S, Schneider, LS, Pawluczyk, S, Spann, BM, Brewer, J, Vanderswag, H, Heidebrink, JL, Lord, JL, Johnson, K, Doody, RS, Villanueva-Meyer, J, Chowdhury, M, Stern, Yaakov, Honig, LS, Bell, KL, Morris, JC, Ances, B, Carroll, M, Leon, S, Mintun, MA, Schneider, S, Marson, D, Griffith, R, Clark, D, Grossman, H, Mitsis, E, Romirowsky, A, deToledo-Morrell, L, Shah, RC, Duara, R, Varon, D, Roberts, P, Albert, M, Onyike, C, Kielb, S, Rusinek, H, de, Leon, MJ, Glodzik, L, De, Santi, S, Doraiswamy, PM, Petrella, JR, Coleman, RE, Arnold, SE, Karlawish, JH, Wolk, D, Smith, CD, Jicha, G, Hardy, P, Lopez, OL, Oakley, M, Simpson, DM, Porsteinsson, AP, Goldstein, BS, Martin, K, Makino, KM, Ismail, MS, Brand, C, Mulnard, RA, Thai, G, Mc-Adams-Ortiz, C, Womack, K, Mathews, D, Quiceno, M, Diaz-Arrastia, R, King, R, Martin-Cook, K, DeVous, M, Levey, AI, Lah, JJ, Cellar, JS, Burns, JM, Anderson, HS, Swerdlow, RH, Apostolova, L, Lu, PH, Bartzokis, G, Silverman, DH, Graff-Radford, NR, Parfitt, F, Johnson, H, Farlow, MR, Hake, AM, Matthews, BR, Herring, S, van, Dyck, CH, Carson, RE, MacAvoy, MG, Chertkow, H, Bergman, H, Hosein, C, Black, S, Stefanovic, B, Caldwell, C, Ging-Yuek, Hsiung, R, Feldman, H, Mudge, B, Assaly, M, Kertesz, A, Rogers, J, Trost, D, Bernick, C, Munic, D, Kerwin, D, Mesulam, MM, Lipowski, K, Wu, CK, Johnson, N, Sadowsky, C, Martinez, W, Villena, T, Turner, RS, Reynolds, B, Sperling, RA, Johnson, KA, Marshall, G, Frey, M, Yesavage, J, Taylor, JL, Lane, B, Rosen, A, Tinklenberg, J, Sabbagh, M, Belden, C, Jacobson, S, Kowall, N, Killiany, R, Budson, AE, Norbash, A, Johnson, PL, Obisesan, TO, Wolday, S, Bwayo, SK, Lerner, A, Hudson, L, Ogrocki, P, Fletcher, E, Carmichael, O, Olichney, J, Kittur, S, Borrie, M, Lee, TY, Bartha, R, Johnson, S, Asthana, S, Carlsson, CM, Potkin, SG, Preda, A, Nguyen, D, Tariot, P, Fleisher, A, Reeder, S, Bates, V, Capote, H, Rainka, M, Scharre, DW, Kataki, M, Zimmerman, EA, Celmins, D, Brown, AD, Pearlson, GD, Blank, K, Anderson, K, Santulli, RB, Schwartz, ES, Sink, KM, Williamson, JD, Garg, P, Watkins, F, Ott, BR, Querfurth, H, Tremont, G, Salloway, S, Malloy, P, Correia, S, Rosen, HJ, Miller, BL, Mintzer, J, Longmire, CF, Spicer, K, Finger, E, Rachinsky, I, Drost, D, Jernigan, T, McCabe, C, Grant, E, Ernst, T, Kuperman, J, Chung, Y, Murray, S, Bloss, C, Darst, B, Pritchett, L, Saito, A, Amaral, D, DiNino, M, Eyngorina, B, Sowell, E, Houston, S, Soderberg, L, Kaufmann, W, van, Zijl, P, Rizzo-Busack, H, Javid, M, Mehta, N, Ruberry, E, Powers, A, Rosen, B, Gebhard, N, Manigan, H, Frazier, J, Kennedy, D, Yakutis, L, Hill, M, Gruen, J, Bosson-Heenan, J, and Carlson, H

Subjects
anatomy & histology, pathology [Visual Cortex], Adult, Diagnostic Imaging, Male, Linkage disequilibrium, Visual perception, genetic structures, Adolescent, Genotype, Imaging genetics, methods [Diagnostic Imaging], Single-nucleotide polymorphism, Genome-wide association study, Saccharomyces cerevisiae, Biology, Polymorphism, Single Nucleotide, Cohort Studies, methods [Brain Mapping], pathology [Brain], Cortex (anatomy), Genetic variation, Medicine and Health Sciences, medicine, Humans, genetics [Phosphoric Diester Hydrolases], Aged, Visual Cortex, Genetics, Brain Mapping, Multidisciplinary, Models, Genetic, Phosphoric Diester Hydrolases, metabolism [Saccharomyces cerevisiae], Brain, Genetic Variation, Genomics, Middle Aged, Biological Sciences, Visual cortex, medicine.anatomical_structure, Female, Genome-Wide Association Study
Abstract

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association ( P combined = 3.2 × 10 −8 ). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10 −9 ) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5′ UTR of GPCPD1 , glycerophosphocholine phosphodiesterase GDE1 homolog ( Saccharomyces cerevisiae ), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Published
2012

7. Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional-executive network function in Alzheimer's disease

Author

Wolk, D. A., Dickerson, B. C., the Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aiello, M., Aisen, P., Albert, M. S., Alexander, G., Anderson, H. S., Anderson, K., Apostolova, L., Arnold, S., Ashford, W., Assaly, M., Asthana, S., Bandy, D., Bartha, R., Bates, V., Beckett, L., Bell, K. L., Benincasa, A. L., Bergman, H., Bernick, C., Bernstein, M., Black, S., Blank, K., Borrie, M., Brand, C., Brewer, J., Brown, A. D., Burns, J. M., Cairns, N. J., Caldwell, C., Capote, H., Carlsson, C. M., Carmichael, O., Cellar, J. S., Celmins, D., Chen, K., Chertkow, H., Chowdhury, M., Clark, D., Connor, D., Correia, S., Crawford, K., Dale, A., de Leon, M. J., De Santi, S. M., DeCarli, C., deToledo-Morrell, L., DeVous, M., Diaz-Arrastia, R., Dolen, S., Donohue, M., Doody, R. S., Doraiswamy, P. M., Duara, R., Englert, J., Farlow, M., Feldman, H., Felmlee, J., Fleisher, A., Fletcher, E., Foroud, T. M., Foster, N., Fox, N., Frank, R., Gamst, A., Given, C. A., Graff-Radford, N. R., Green, R. C., Griffith, R., Grossman, H., Hake, A. M., Hardy, P., Harvey, D., Heidebrink, J. L., Hendin, B. A., Herring, S., Honig, L. S., Hosein, C., Robin Hsiung, G.-Y., Hudson, L., Ismail, M. S., Jack, C. R., Jacobson, S., Jagust, W., Jayam-Trouth, A., Johnson, K., Johnson, H., Johnson, N., Johnson, K. A., Johnson, S., Kachaturian, Z., Karlawish, J. H., Kataki, M., Kaye, J., Kertesz, A., Killiany, R., Kittur, S., Koeppe, R. A., Korecka, M., Kornak, J., Kozauer, N., Lah, J. J., Laubinger, M. M., Lee, V. M.- Y., Lee, T.- Y., Lerner, A., Levey, A. I., Longmire, C. F., Lopez, O. L., Lord, J. L., Lu, P. H., MacAvoy, M. G., Malloy, P., Marson, D., Martin-Cook, K., Martinez, W., Marzloff, G., Mathis, C., Mc-Adams-Ortiz, C., Mesulam, M., Miller, B. L., Mintun, M. A., Mintzer, J., Molchan, S., Montine, T., Morris, J., Mulnard, R. A., Munic, D., Nair, A., Neu, S., Nguyen, D., Norbash, A., Oakley, M., Obisesan, T. O., Ogrocki, P., Ott, B. R., Parfitt, F., Pawluczyk, S., Pearlson, G., Petersen, R., Petrella, J. R., Potkin, S., Potter, W. Z., Preda, A., Quinn, J., Rainka, M., Reeder, S., Reiman, E. M., Rentz, D. M., Reynolds, B., Richard, J., Roberts, P., Rogers, J., Rosen, A., Rosen, H. J., Rusinek, H., Sabbagh, M., Sadowsky, C., Salloway, S., Santulli, R. B., Saykin, A. J., Scharre, D. W., Schneider, L., Schneider, S., Schuff, N., Shah, R. C., Shaw, L., Shen, L., Silverman, D. H. S., Simpson, D. M., Sink, K. M., Smith, C. D., Snyder, P. J., Spann, B. M., Sperling, R. A., Spicer, K., Stefanovic, B., Stern, Yaakov, Stopa, E., Tang, C., Tariot, P., Taylor-Reinwald, L., Thai, G., Thomas, R. G., Thompson, P., Tinklenberg, J., Toga, A. W., Tremont, G., Trojanowki, J. Q., Trost, D., Turner, R. S., van Dyck, C. H., Vanderswag, H., Varon, D., Villanueva-Meyer, J., Villena, T., Walter, S., Wang, P., Watkins, F., Williamson, J. D., Wolk, D., Wu, C.-K., Zerrate, M., and Zimmerman., E. A.

Published
2010
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8. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

Author

Ho, A. J., Stein, J. L., Hua, X., Lee, S., Hibar, D. P., Leow, A. D., Dinov, I. D., Toga, A. W., Saykin, A. J., Shen, L., Foroud, T., Pankratz, N., Huentelman, M. J., Craig, D. W., Gerber, J. D., Allen, A. N., Corneveaux, J. J., Stephan, D. A., DeCarli, C. S., DeChairo, B. M., Potkin, S. G., Jack, C. R., Weiner, M. W., Raji, C. A., Lopez, O. L., Becker, J. T., Carmichael, O. T., Thompson, P. M., the Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Thal, L., Petersen, R., Jagust, W., Trojanowki, J., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.- Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given II, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., and Wilks, K. L.

Published
2010
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9. Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

Author

Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jack CR.<Suffix>Jr</Suffix>, Jagust, W., Trojanowki, JQ., Toga, AW., Beckett, L., Green, RC., Saykin, AJ., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, RG., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Bandy, D., Koeppe, RA., Foster, N., Reiman, EM., Chen, K., Mathis, C., Cairns, NJ., Taylor-Reinwald, L., Shaw, L., Lee, VM., Korecka, M., Crawford, K., Neu, S., Foroud, TM., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, PJ., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, LS., Pawluczyk, S., Spann, BM., Brewer, J., Vanderswag, H., Heidebrink, JL., Lord, JL., Johnson, K., Doody, RS., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, LS., Bell, KL., Morris, JC., Ances, B., Carroll, M., Leon, S., Mintun, MA., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, RC., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon MJ., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, JR., Coleman, R., Arnold, SE., Karlawish, JH., Wolk, D., Smith, CD., Jicha, G., Hardy, P., Lopez, OL., Oakley, M., Simpson, DM., Porsteinsson, AP., Goldstein, BS., Martin, K., Makino, KM., Ismail, M., Brand, C., Mulnard, RA., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Martin-Cook, K., DeVous, M., Levey, AI., Lah, JJ., Cellar, JS., Burns, JM., Anderson, HS., Swerdlow, RH., Apostolova, L., Lu, PH., Bartzokis, G., Silverman, DH., Graff-Radford, NR., Parfitt, F., Johnson, H., Farlow, MR., Hake, AM., Matthews, BR., Herring, S., van Dyck CH., Carson, RE., MacAvoy, MG., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, GY., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, MM., Lipowski, K., Wu, CK., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, RS., Reynolds, B., Sperling, RA., Johnson, KA., Marshall, G., Frey, M., Yesavage, J., Taylor, JL., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, AE., Norbash, A., Johnson, PL., Obisesan, TO., Wolday, S., Bwayo, SK., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, TY., Bartha, R., Johnson, S., Asthana, S., Carlsson, CM., Potkin, SG., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, DW., Kataki, M., Zimmerman, EA., Celmins, D., Brown, AD., Pearlson, GD., Blank, K., Anderson, K., Santulli, RB., Schwartz, ES., Sink, KM., Williamson, JD., Garg, P., Watkins, F., Ott, BR., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, HJ., Miller, BL., Mintzer, J., Longmire, CF., Spicer, K., Finger, E., Rachinsky, I., Drost, D., Dukart, J., Kherif, F., Mueller, K., Adaszewski, S., Schroeter, M.L., Frackowiak, R.S., Draganski, B., Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Aisen, P., Petersen, R., Jack CR.<Suffix>Jr</Suffix>, Jagust, W., Trojanowki, JQ., Toga, AW., Beckett, L., Green, RC., Saykin, AJ., Morris, J., Liu, E., Montine, T., Gamst, A., Thomas, RG., Donohue, M., Walter, S., Gessert, D., Sather, T., Harvey, D., Kornak, J., Dale, A., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., DeCarli, C., Bandy, D., Koeppe, RA., Foster, N., Reiman, EM., Chen, K., Mathis, C., Cairns, NJ., Taylor-Reinwald, L., Shaw, L., Lee, VM., Korecka, M., Crawford, K., Neu, S., Foroud, TM., Potkin, S., Shen, L., Kachaturian, Z., Frank, R., Snyder, PJ., Molchan, S., Kaye, J., Quinn, J., Lind, B., Dolen, S., Schneider, LS., Pawluczyk, S., Spann, BM., Brewer, J., Vanderswag, H., Heidebrink, JL., Lord, JL., Johnson, K., Doody, RS., Villanueva-Meyer, J., Chowdhury, M., Stern, Y., Honig, LS., Bell, KL., Morris, JC., Ances, B., Carroll, M., Leon, S., Mintun, MA., Schneider, S., Marson, D., Griffith, R., Clark, D., Grossman, H., Mitsis, E., Romirowsky, A., deToledo-Morrell, L., Shah, RC., Duara, R., Varon, D., Roberts, P., Albert, M., Onyike, C., Kielb, S., Rusinek, H., de Leon MJ., Glodzik, L., De Santi, S., Doraiswamy, P., Petrella, JR., Coleman, R., Arnold, SE., Karlawish, JH., Wolk, D., Smith, CD., Jicha, G., Hardy, P., Lopez, OL., Oakley, M., Simpson, DM., Porsteinsson, AP., Goldstein, BS., Martin, K., Makino, KM., Ismail, M., Brand, C., Mulnard, RA., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Martin-Cook, K., DeVous, M., Levey, AI., Lah, JJ., Cellar, JS., Burns, JM., Anderson, HS., Swerdlow, RH., Apostolova, L., Lu, PH., Bartzokis, G., Silverman, DH., Graff-Radford, NR., Parfitt, F., Johnson, H., Farlow, MR., Hake, AM., Matthews, BR., Herring, S., van Dyck CH., Carson, RE., MacAvoy, MG., Chertkow, H., Bergman, H., Hosein, C., Black, S., Stefanovic, B., Caldwell, C., Hsiung, GY., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Munic, D., Kerwin, D., Mesulam, MM., Lipowski, K., Wu, CK., Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, RS., Reynolds, B., Sperling, RA., Johnson, KA., Marshall, G., Frey, M., Yesavage, J., Taylor, JL., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M., Belden, C., Jacobson, S., Kowall, N., Killiany, R., Budson, AE., Norbash, A., Johnson, PL., Obisesan, TO., Wolday, S., Bwayo, SK., Lerner, A., Hudson, L., Ogrocki, P., Fletcher, E., Carmichael, O., Olichney, J., Kittur, S., Borrie, M., Lee, TY., Bartha, R., Johnson, S., Asthana, S., Carlsson, CM., Potkin, SG., Preda, A., Nguyen, D., Tariot, P., Fleisher, A., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, DW., Kataki, M., Zimmerman, EA., Celmins, D., Brown, AD., Pearlson, GD., Blank, K., Anderson, K., Santulli, RB., Schwartz, ES., Sink, KM., Williamson, JD., Garg, P., Watkins, F., Ott, BR., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, HJ., Miller, BL., Mintzer, J., Longmire, CF., Spicer, K., Finger, E., Rachinsky, I., Drost, D., Dukart, J., Kherif, F., Mueller, K., Adaszewski, S., Schroeter, M.L., Frackowiak, R.S., and Draganski, B.

Abstract

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

Published
2013

11. Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia.

Author

Ryzhikova E, Kazakov O, Halamkova L, Celmins D, Malone P, Molho E, Zimmerman EA, and Lednev IK

Subjects
Aged, Case-Control Studies, Diagnosis, Differential, Female, Humans, Male, Neural Networks, Computer, Sensitivity and Specificity, Alzheimer Disease blood, Alzheimer Disease diagnosis, Spectrum Analysis, Raman
Abstract

The key moment for efficiently and accurately diagnosing dementia occurs during the early stages. This is particularly true for Alzheimer's disease (AD). In this proof-of-concept study, we applied near infrared (NIR) Raman microspectroscopy of blood serum together with advanced multivariate statistics for the selective identification of AD. We analyzed data from 20 AD patients, 18 patients with other neurodegenerative dementias (OD) and 10 healthy control (HC) subjects. NIR Raman microspectroscopy differentiated patients with more than 95% sensitivity and specificity. We demonstrated the high discriminative power of artificial neural network (ANN) classification models, thus revealing the high potential of this developed methodology for the differential diagnosis of AD. Raman spectroscopic, blood-based tests may aid clinical assessments for the effective and accurate differential diagnosis of AD, decrease the labor, time and cost of diagnosis, and be useful for screening patient populations for AD development and progression. Multivariate data analysis of blood serum Raman spectra allows for the differentiation between patients with Alzheimer's disease, other types of dementia and healthy individuals., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2015
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12. Evaluation of a prototype point-of-care instrument based on monochromatic x-ray fluorescence spectrometry: potential for monitoring trace element status of subjects with neurodegenerative disease.

Author

McIntosh KG, Cusack MJ, Vershinin A, Chen ZW, Zimmerman EA, Molho ES, Celmins D, and Parsons PJ

Subjects
Aged, Alzheimer Disease blood, Alzheimer Disease urine, Case-Control Studies, Copper blood, Copper urine, Female, Humans, Male, Neurodegenerative Diseases urine, Parkinson Disease blood, Parkinson Disease urine, Selenium blood, Selenium urine, Sensitivity and Specificity, Spectrometry, X-Ray Emission methods, Trace Elements urine, Zinc blood, Zinc urine, Neurodegenerative Diseases blood, Point-of-Care Systems, Spectrometry, X-Ray Emission instrumentation, Trace Elements blood
Abstract

Assessment of trace elements such as Cu, Zn, and Se in patients with neurodegenerative disease, such as Alzheimer's (AD) and Parkinson's disease (PD), may be useful in etiologic studies and in assessing the risk of developing these conditions. A prototype point-of-care (POC) instrument based on monochromatic x-ray fluorescence (M-XRF) was assembled and evaluated for the determination of Cu, Zn, and Se in whole blood, plasma, and urine. The prototype instrument was validated using certified reference materials for Cu and Zn in serum/plasma, and the reported bias and relative imprecision were <10%. The M-XRF prototype performance was further assessed using human specimens collected from AD and PD subjects, and was found to be satisfactory (<20% bias) for monitoring Cu and Zn levels in plasma and whole blood. However, the prototype M-XRF sensitivity was not sufficient for quantifying Cu, Zn, or Se in urine. Nonetheless, while validating the prototype instrument, body fluids (whole blood, plasma, and urine) were collected from 19 AD patients, 23 PD patients, and 24 controls specifically for trace element analysis using well-validated methods based on inductively coupled plasma mass spectrometry (ICP-MS). This limited biomonitoring study provided robust data for up to 16 elements including Sb, As, Ba, Cd, Cs, Co, Cr, Cu, Hg, Pb, Mo, Se, Tl, Sn, Zn, and U in plasma, whole blood, and urine. The results did not indicate any significant differences in most trace elements studied between AD or PD patients compared to controls, although the sample size is limited. A statistically significant increase in plasma Se was identified for PD patients relative to AD patients, but this could be due to age differences.

Published
2012
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